Diisopropylethylamine → HCID 72944227, compound

HRID 1505702Notes

Reaction equation

HRID 1505702 reaction equation
[O:1]1[CH:3]([C:4]([F:7])([F:6])[F:5])[CH2:2]1.Cl.[CH3:9][N:10]1[CH:14]=[C:13]([C:15]2[CH:16]=[C:17]([C:21]3[N:26]=[CH:25][C:24]([C:27]4[CH:28]=[N:29][N:30]([CH:32]5[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]5)[CH:31]=4)=[CH:23][N:22]=3)[CH:18]=[CH:19][CH:20]=2)[CH:12]=[N:11]1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:5][C:4]([F:7])([F:6])[CH:3]([OH:1])[CH2:2][N:35]1[CH2:34][CH2:33][CH:32]([N:30]2[CH:31]=[C:27]([C:24]3[CH:25]=[N:26][C:21]([C:17]4[CH:18]=[CH:19][CH:20]=[C:15]([C:13]5[CH:12]=[N:11][N:10]([CH3:9])[CH:14]=5)[CH:16]=4)=[N:22][CH:23]=3)[CH:28]=[N:29]2)[CH2:37][CH2:36]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5207692-(Trifluoromethyl)oxiraneHCID 89924162HCID 89924162, compound

Product 1

HCID 72944227HCID 72944227, compoundYield 36.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

1,2-Epoxy-3,3,3-trifluoropropane(84 mg; 0.72 mmol; 2.4 eq.) was added to a solution of 2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyrimidine (example 1, 200 mg; 0.31 mmol; 1.0 eq.) and DIEA (53 μl; 0.31 mmol; 1.0 eq.) in DMF (4 mL). The reaction mixture was stirred at 50° C. O/N. It was then diluted with water and extracted with EtOAc (three times). Combined organic phases were washed with water and brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM:EtOAc, gradient from 40:60 to 0:100) afforded the title compound as a beige powder (56 mg, 36%). 1H NMR (300 MHz, DMSO-d6) δ 9.17 (s, 2H), 8.59-8.49 (m, 2H), 8.27 (s, 1H), 8.25-8.18 (m, 1H), 8.14 (s, 1H), 7.93 (s, 1H), 7.75-7.67 (m, 1H), 7.52 (t, J=7.7 Hz, 1H), 6.24-6.13 (m, 1H), 4.28-4.08 (m, 2H), 3.90 (s, 3H), 3.12-2.97 (m, 2H), 2.66-2.53 (m, 2H), 2.36-2.17 (m, 2H), 2.12-1.86 (m, 4H). HPLC (Condition A): Rt 2.85 min (purity 98.4%). MS (ESI+): 498.4.

Workup

  1. extractionextracted with EtOAc (three times)
  2. washCombined organic phases were washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica (DCM:EtOAc, gradient from 40:60 to 0:100)

Sources & evidence

ORD record
ord-3fed371bc61344b1aa7ce9e69a588ef4
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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